To effectively combat disease, a vaccine should ideally stimulate several immunological reactions, such as the production of antibodies (humoral immunity) and the mobilization of immunological cells (cellular immunity).
A cellular immune response brings about a proliferation and stimulation of T-lymphocytes, such as cytotoxic (CTL) and delayed-type hypersensitivity (DTH) T-cells, which go on to activate macrophages and impede the propagation of pathogens. The induction of a humoral response causes the body's B-cells to produce antibodies against the offending pathogen. However, some intracellular pathogens and retroviruses survive and are extremely resistant to humoral-based immune responses and require the stimulation of cytotoxic T-cells to destroy such biological invaders.
Synthetic peptides are often used as antigenic epitopes and can be tailor-made using standard peptide synthesis technologies so that they induce minimal side effects. However, such peptides typically invoke a relatively weak immunogenic response.
Nonetheless, immunogenicity can be boosted by attaching a lipid to the synthetic peptide. It has been shown, for example, that lipidation of synthetic peptide antigens leads to the induction of strong T-cell proliferation, CTL, and antibody responses in immunized mice, chimpanzees, or humans (BenMohamed et al., Vaccine, 18, 2843-2855 (2000); Gahery-Segard et al., J. Virology., 74, 1694-1703 (2000); Seth et al., AIDS Res. Hum. Retroviruses, 16, 337-343 (2000); Tsunoda et al., Vaccine, 17, 675-685 (1999); BenMohamed et al., Eur. J. Immunol, 27, 1242-1253 (1997); Vitiello et al., J. Clin. Invest., 95, 341-349 (1995)).
A preparation of such antigens may be delivered in vivo using a vaccine “carrier,” but the carrier itself can become the target of the host's humoral immune response. Thus, the host's antibodies act against the vaccine carrier and not the antigenic epitope, which can result in rapid clearance of the vaccine by anti-carrier antibodies, negating the usefulness of the actual vaccine.
The incorporation of the lipid moiety of a lipopeptide into a liposome, however, proves an extremely useful way in which to deliver an antigen in vivo without eliciting an immune response against the carrier. However, none of these advances assist in the modulation of one immune response to another. That is, it has not previously been shown that a liposomally-bound lipopeptide can elicit cellular and humoral immune responses by altering the number of lipids attached to a single peptide.
The present invention, however, provides a novel way of invoking and modulating between cellular and humoral immune responses by using a single antigenic peptide and a carrier that does not stimulate humoral responses against itself.